Abstract 15
Category: Clinical Science
At the end of the session, participants will be able to:
- Understand the implications of CDKN2A/B homozygous deletion in different neoplasms.
- Recognize the various methods for detecting CDKN2A/B homozygous deletion.
COI Disclosure:
None to disclose.
Presenter
Karina Martin is a PGY-5 Neuropathology Resident at the University of British Columbia.
Karina C. Martin, MD1,2, Tara Spence, PhD1,2, Janine Senz, BMLSc2, Julia Naso, MD, PhD1,2, Andrew Churg, MD1,2, Stephen Yip, MD1,2
1Department of Pathology, Vancouver General Hospital
2Department of Pathology and Laboratory Medicine, University of British Columbia Vancouver, BC Canada
Target Audience:
Pathologists, Residents, Medical Students
CanMEDS:
Medical Expert (the integrating role), Collaborator, Leader
Chromogenic in situ hybridization for detection of CDKN2A/B homozygous deletion
Abstract
The presence of CDKN2A/B homozygous deletion (HD) denotes a higher WHO grade and more aggressive behavior in gliomas and meningiomas. The gold standard assays for detecting copy number variation (CNV) include chromosomal microarray, next generation sequencing, and fluorescence in situ hybridization (FISH). However, these methods are costly, time consuming, and have limited availability in resource-sparse centers. Thus, an inexpensive and time-efficient assay for detecting CDKN2A/B HD would be helpful for routine neuropathology cases.
Chromogenic in situ hybridization (CISH) combines DNA hybridization techniques utilized in FISH with conventional peroxidase reactions utilized in immunohistochemistry to interrogate CNV with brightfield microscopy. We hypothesize that CISH is a sensitive and specific method for detecting CDKN2A/B HD.
We performed CDKN2A CISH on a retrospective cohort of whole slide tissue sections of 5 gliomas and 10 meningiomas using the ABNOVA CDKN2A/CEP9 CISH probes and implementation kit. Two pathologists independently counted and scored 100 cells from each case showing any CEP9 (red/control) signals and no CDKN2A (green) signals as HD, and cells showing both red and green signals as CDKN2A/B intact. The pathologists’ scores were averaged and compared to the CDKN2A/B status for each of the glioma and meningioma cases, acquired via FISH testing and methylation profiling, respectively.
Our results demonstrate that detection of CDKN2A/B HD with CISH showed high concordance with CDKN2A/B locus interrogation with orthogonal assays. CISH is a sensitive and specific method for detecting CDKN2A/B HD in glioma and meningioma and is a more cost-effective and practical alternative to traditional CNV detection methods.